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Background Potential interaction between nebivolol, a unique antihypertensive which couples vascular endothelial nitric oxide releasing capabilities with cardioselective β1-blockade, and furosemide, was studied by comparison of pharmacokinetic (PK) parameter estimates in subjects genotyped for CYP2D6 status. Methods Subjects[12 extensive (EM), 3 poor (PM) metabolizers] received 40 mg oral furosemide on Day 1. On Days 2–10, oral nebivolol (10 mg) was administered QD. On Day 11, nebivolol and furosemide were given QD. PK estimates for nebivolol and furosemide were assessed. Results Co-administration of furosemide with nebivolol produced no statistically significant changes in PK estimates for d,l-nebivolol or its enantiomers in EM and PM subjects. The 90% confidence intervals for Cmax, CSS and AUCτ in EM and PM subjects were within 80% - 125%. For furosemide, ANOVA testing of Cmax, AUCt, AUC∞, and Cl/F revealed no interaction with nebivolol. The 90% confidence intervals for furosemide Cmax, AUCt and AUC∞ were slightly different between treatments, but all passed through 100% and least squares mean ratios ranged from 0.93 to 0.95. Conclusions Regardless of CYP2D6 metabolizing status, there were no drug interactions observed that would affect the PK profile of either nebivolol or furosemide upon co-administration. Clinical Pharmacology & Therapeutics (2005) 77, P79–P79; doi: 10.1016/j.clpt.2004.12.192 |
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